Bronchopulmonary System Research Articles

Distribution of polymorphic variants of the mannose-binding lectin gene (MBL2) in children with mild and severe asthma

Asthma is one of the most common inflammatory diseases in the world. One of the factors in the development of this disease is a low concentration of mannose-binding lectin (MBL), encoded by the MBL2 gene. Purpose. To study the distribution of genotypes and alleles of polymorphic variants of the MBL2 gene in children with asthma. Material and methods. The study included children with diagnosed bronchial asthma (n=400) (Krasnoyarsk). The control group consisted of children comparable in gender and age to the patients (n=229) and newborns (n=302). GINA-202 guidelines were used to determine the severity of the disease. Results. Statistically significant differences were identified for polymorphisms localized in the first exon of the gene – rs1800450 and rs1800451. A low occurrence of the BB rs1800450 genotype in sick and healthy children was revealed, which may be associated with early mortality or disability due to severe infections with severe MBL deficiency. Homozygotes for the mutant allele C of the rs1800451 MBL2 polymorphism were not found in any of the comparison groups, which indicates a rare distribution of this allele in Caucasian populations. Conclusion. The present study showed that polymorphisms in the MBL2 gene play a predisposing role in the development of diseases of the bronchopulmonary system using the example of asthma.

Elecampane: a review of the pharmacological effects of active substances in diseases of the bronchopulmonary system

Chronic diseases of the bronchopulmonary system have reached epidemic levels worldwide, and the situation is deteriorating as the degree of urbanization increases. Elecampane is called Russian ginseng, because the active ingredients of its roots have a multifaceted effect on the body. In diseases of the bronchopulmonary system, they promote expectoration of sputum, stimulate blood circulation and saturate the blood with oxygen, have an immunomodulatory effect, which helps to fight viral and bacterial infections of the lungs. Especially relevant is the use of elecampane preparations for the treatment of pulmonary tuberculosis, mycoplasma respiratory infection and viral infections such as COVID-19, herpesviruses, which can provoke serious lung changes, including pneumatic fibrosis and pneumosclerosis, which are formed within three months or more, and the resulting fibrosis foci are not subject to involution. Meanwhile at the stage of development of the process, fibrous changes can be minimized by both drug and phytotherapy treatment. The antiviral effect of elecampane preparations may play a role in modifying or slowing the progression of pulmonary fibrosis, especially when used at an early stage. In bronchial asthma, elecampane preparations can weaken the immuneinflammatory response.

ОСОБЕННОСТИ НУТРИТИВНОГО СТАТУСА ДЕТЕЙ С МУКОВИСЦИДОЗОМ РАЗЛИЧНЫХ ЭТНИЧЕСКИХ ГРУПП СЕВЕРНОГО КАВКАЗА

Adequate nutritional status in a patient with cystic fibrosis (CF) positively correlates with the normal function of the bronchopulmonary system. Many domestic and foreign studies have been conducted so far to assess the nutritional status of children and adults with CF. However, there is no data as yet on the phenotypic characteristics of children from different ethnic groups of the North Caucasus depending on their genotype. The purpose of this research was to study the peculiarities of nutritional status in children with CF of the following Russia’s North Caucasus ethnic groups: Chechen, Karachay-Circassian, Dagestani, Ingush and Ossetian-Alanian. Materials and methods used: a single-center open prospective study of 117 children with CF aged 2 months to 17 years old (Me 6 y/o) of various North Caucasus ethnic groups was conducted. All patients have undergone molecular diagnosis and assessment of both nutritional status and exocrine pancreatic function. Results: 50.4% of pediatric patients with CF in the Russia’s North Caucasus have had pathological mutations in c.1545_1546delTA, p.(Tyr515*) and c.3846G>A, p.(Trp1282*) in homozygous state. These mutations were most often found in the Ingush (100%) and Chechen (82%) ethnic groups and somewhat less frequently in the Dagestani (57.1%) and Karachay-Circassian (54%) ethnic groups. In the Chechen and Ossetian-Alanian ethnic groups, when these mutations were detected, severe pancreatic insufficiency was established in 40.5% and 100% of cases, respectively. Pseudo-Bartter syndrome was diagnosed in 60% of cases with this genetic variant in a homozygous or compound heterozygous states during the patients’ first years of life. Indicators for the nutritional status of children with CF from different ethnic groups were significantly lower compared to those recorded officially in the 2021 Russian National Register of Patients with CF. Conclusion: it is necessary to study the course of CF and the state of nutritional status separately in each population and its connection with the identified genetic characteristics of the Russia’s North Caucasus ethnic groups. The genotype and phenotype patterns for these patients were the reason for the development of disorders of the exocrine function of the pancreas and pseudo-Bartter syndrome at an early age, which in its turn could lead to further development of nutritional deficiency.

Chronic adenoiditis and its effect on the reactivity of the bronchopulmonary system, the possibility of non-drug correction

Introduction. In pediatric otorhinolaryngological practice, chronic adenoiditis is one of the most common diseases and causes the search for additional and effective methods of treatment.Aim. To evaluate the clinical effectiveness of the use of aqueous solutions treated with low-frequency ultrasound with high specific energy and monochromatic light radiation in the complex therapy of chronic adenoiditis in children.Materials and methods. The number of participants in the study was 104 patients aged 4 to 15 years with a verified diagnosis of chronic adenoiditis and were divided into 3 groups depending on the treatment. A comparative analysis of the results obtained was carried out before the start of therapy (day 0) and on the 7th day after the treatment. The state of the nasopharynx was assessed using a flexible nasopharyngoscope, as well as the structure of the middle ear and auditory tube during acoustic impedancemetry.Results. The use of a course of treatment of low-frequency ultrasonic cavitation in combination with photochromotherapy made it possible to relieve the signs of chronic adenoiditis in 62% of cases (p < 0.001), reduce the number of patients with grade III adenoid hypertrophy by 54% (p = 0.035), and reduce by 2 times (p = 0.05) number of relapses of chronic adenoiditis. In the group of children using low-frequency ultrasonic cavitation, the positive effect of treatment was 3.3 times [CI 0.75; 14.6] higher compared to the control group, and in combination with photochromotherapy it was 3.6 times [CI 0.85; 15.5]. The absence of adenotomy was assessed as a positive effect.Conclusion. The data obtained showed that the inclusion of non-drug methods of physical influence (low-frequency ultrasonic cavitation both in monotherapy and in combination with photochromotherapy) in complex treatment can reduce the number of surgical interventions on the organs of the lymphopharyngeal ring – the pharyngeal tonsil.

MORPHORANGENOLOGICAL CHARACTERISTICS IN EARLY DIAGNOSIS OF CHILDREN WITH INFLAMMATORY PULMONARY DISEASES

The choice of this particular topic is due to the need to study morphofunctional studies and compare them with radiological data. The literature shows that in order to improve and timely diagnosis and prevention of inflammatory diseases of the bronchopulmonary system, the director carries out radiological diagnostic methods. Morphological studies of pleural fluid can affect the diagnosis and treatment of children with pneumonia.

#1073 Changes in endothelial function in patients with impaired central and renal hemodynamics respiratory pathology

Abstract Background and Aims To determine the degree of influence of endothelial dysfunction on the hemodynamics of renal and central vessels in respiratory pathology, as well as to determine the effectiveness of complex therapy regimens with carvedilol. Method Studies were conducted in 26 patients with chronic obstructive pulmonary disease (COPD) of II- III severity (group 1, in whom the level of glomerular filtration rate of the kidneys eGFR CKD-EPI ≥6 ml/min/1.73 m2 was determined) and 32 patients with COPD of IV severity (group 2, they were determined e GFR CKD-EPI ≥60 ml/min/1.73 m2). Patients received one course of ten-day standard therapy (GOLD, 2020) in combination with a beta–blocker drug, T. carvedilol 5 mg (Vertex). Doppler echocardiographic examination of peripheral vessels, heart and renal vessels of patients was performed. Stable metabolites of nitric oxide (Cm NO) in blood plasma, ventilation and perfusion state of the lungs were determined. Results A significant decrease in the functional state of the respiratory system was parallel with a decrease in Cm NO synthesis, which was clearly reflected in the second group (by 11%) compared with the first group (by 7%). Pronounced structural changes with remodeling of the right parts of the heart, as well as a pronounced degree of pancreatic hypertrophy in the second group were accompanied by a sharp change in renal filtration function (eGFR ≤60 ml/min/1.73 m2). When measuring the state of diastolic dysfunction of the right parts of the heart, a decrease in E/As well as an increase in the circulatory vascular resistance index and mean blood pressure were significantly higher in the first group of patients (where еGFR ≥6 ml/min/1.73 m2). After a course of treatment with t. carvedilol, based on basic treatment, normalization of endothelial function was determined, reflected in an increase in the concentration of stable metabolites of nitric oxide by 1.05 and 1.5 times (p<0.05) in the biological fluid, respectively, in the first and second groups. In the dynamics of the course of therapy in groups of patients with 75% and 35% decrease in lung ventilation capacity, mean pulmonary arterial pressure decreased by 18.1 and 14.3%, respectively, and the hemodynamic resistance index decreased by 7.9% and 5.7% in parallel (p<0.05). Conclusion When monitoring the functional state of central and renal hemodynamics and ventilation-perfusion function of the bronchopulmonary system after complex treatment with carvedilol, a long-term hypotensive effect, a decrease in endothelial dysfunction, respectively, and an improvement in central and renal hemodynamics were determined.

Changes in autonomic regulation in workers under conditions of long-term fluoride intoxication

Introduction. Long-term intake and accumulation of fluoride compounds in the body, in addition to pathological changes in the bronchopulmonary system, bone tissue, liver, leads to changes in the regulatory systems, primarily the autonomic ones, in the conditions of chronic fluoride intoxication. The aim of the study was to assess the nature and severity of the changes in autonomic regulation in workers of the main occupations in aluminum production under exposure to chronic fluoride intoxication. Material and methods. We examined fifty two male workers of aluminum production over the age range from 40 to 56 years; work experience was more than 15 years. Autonomic regulation was assessed using spectral analysis of the heart rate variability, highlighting oscillations in the ranges of very low frequency (0.004–0.08 Hz), low (0.09–0.16 Hz), and high frequencies (0.17–0.5 Hz). Results. Analysis of the heart rate variability made it possible to identify 4 groups of subjects: 16 individuals had a moderate decrease in variability and a predominance of low-frequency oscillations, 12 subjects examined cases had a pronounced decline in variability in all frequency ranges; a decrease in the capabilities of autonomic regulation was manifested during a test with hyperventilation by an increase in very low frequency oscillations frequency indicating the need for activation of suprasegmental autonomic centers. In 24 subjects, the stable predominance of low-frequency oscillations indicates an enhancement in sympathetic influence. In response to the hyperventilation test, most of them (18 subjects were included in the group 3) showed an increase in low and very low frequency oscillations as a sign of a violation of baroreceptor regulation. Limitations. The study was limited by the number of workers with long-term work experience in aluminum production who underwent an in-depth medical examination. Conclusion. Changes in autonomic regulation are observed in the majority of aluminum production workers with long-term work experience, which gives grounds to recommend a study of neurovegetative status using heart rate variability analysis during preventive examinations to identify individuals at high risk of developing comorbid diseases.

Epidemiological profile of neuroendocrine tumors in adults in Brazil.

Neuroendocrine tumors (NETs) are a set of diseases that originate from neuroendocrine cells, which comprises a diffuse endocrine system present in various organs of the body. These tumors are more frequent in the gastrointestinal tract (70%) and the bronchopulmonary system (20%-30%). A NET incidence rate of 1-5 per 100,000 inhabitants has been estimated for several European countries and the USA employing 20 years of data. However, no comprehensive studies on this rare neoplasm are available in Brazil. In this context, the aim of this study was to characterize the epidemiological NET profile in the country. This is a retrospective descriptive observational study based on data from Hospital Cancer Records available at the Brazilian National Cancer Institute and the São Paulo Oncocentro Foundation. Demographic, clinical and treatmentrelated variables were analyzed from selected cases employing descriptive statistics. A total of 15,859 cases were identified, most occurring in males (53.4%) and in individuals under 65 years old (63.3%). Small cell carcinoma was the most frequent histological type (46.7%). Bronchopulmonary tumors were the most frequent NETs, followed by pancreatic tumors, with cases mostly concentrated in high complexity centers in the Brazilian Southeast and treated mainly with surgery and chemotherapy, with over half of the patients diagnosed in advanced stages of the disease.

Interdisciplinary approach to diagnosis of life-threatening form of albinism: Germanic-Pudlac syndrome case type 1

The Hermansky-Pudlak syndrome (OMIM#203300) is a hereditary genetically heterogeneous disease with an autosomal recessive type of inheritance. There are 11 clinical-genetic subtypes with similar clinical manifestations, but some type may difference with each other clinically. The most common is type 1 Hermansky-Pudlak syndrome. Purpose: Describe the features of the clinical picture and diagnosis of Hermansky-Pudlak syndrome type 1. Materials and methods: complex clinic-instrumental and molecular-genetic results from 2 patients from one family with incoming diagnosis of albinism are used. Result: An interdisciplinary approach to the diagnosis of albinism and a step-by-step molecular-genetic study help to verify the clinical-genetic diagnosis in a family. The clinical case demonstrated clinical polymorphism within one family. Two patients have similar dermatological and ophthalmological clinical picture, but have difference in bronchopulmonary system and the blood system. Probang-female has a history of prolonged repeated bleeding, coagulogram changes, obstructive bronchitis, albino phenotype and eyes failure. Her brother has a similar albino phenotype and eyes failure. The pathogenic variant NM_000195.5: c.1189del was revealed in a homozygous state in 13 exon of the HPS1 gene and Hermansky-Pudlak syndrome type 1 was confirmed by molecular analysis. Conclusion: On the example of this clinical observation of a family with Hermansky-Pudlak syndrome 1 type features of differential diagnosis of albinic states are shown, it is noted that complex examination of patients is necessary, molecular-diagnostics genetic analysis and constant follow up of a hematologist, ophthalmologist, pulmonologist, allergologist, dermatologist, gastroenterologist, geneticist and pediatrician.

Enteral formulas for nutritional support of patients with cystic fibrosis

Cystic fibrosis (CF) is a hereditary disease characterized by impaired functioning of the glands of external secretion, the phenomena of maldigestion, malabsorption, chronic inflammation in the bronchopulmonary system, which negatively affects the nutritional status. Among patients with CF, regardless of age, there is a high prevalence of malnutrition, which has a multifactorial nature and leads to somatic and psychological consequences, significantly worsens the course and prognosis of the disease, and reduces the quality of life. The high-risk group consists of adolescent children due to the increased energy needs of the body during this period and the progression of the severity of the disease with age. A good nutritional status (NS) is an important parameter for successful control of the CF flow. General dietary recommendations for CF include an increased energy value of food (up to 200% of the target values of kca /day for healthy individuals) while taking pancreatic enzymes. An increased intake of protein, fat, salt, and fat-soluble vitamins is recommended. Important nutritional factors are polyunsaturated fatty acids, fiber, pre-probiotics, trace elements, and antioxidants. It is necessary to take preventive measures to prevent the development of malnutrition and timely correct existing deficiencies, taking into account the individual characteristics of the patient. For this purpose, specialized therapeutic nutrition is used. A wide range of such products in the form of ready-made (drinks, yoghurts, creamy products) or dry mixes to increase the energy and biological value of the actual diet is the best option for correcting the nutritional needs of patients with CF. They have proven clinical efficacy and safety, are well absorbed and tolerated, convenient and easy to use for patients, which significantly increases compliance and improves the result of treatment. The available assortment allows you to choose a personalized approach to each patient, taking into account the general condition, age, existing complications, and associated diseases. The review highlights the causes of nutritional deficiency, changes in approaches to diet therapy against the background of targeted therapy, enteral nutrition products recommended for patients with MV in the territory of the Russian Federation and indications for their appointment.

Metapneumovirus infection in children in modern conditions: clinical and immunological parallels

Aim. The study of metapneumovirus infection clinical and immunological features in children of different ages. Patients and methods. An analysis of 22 patients with mono-metapneumovirus infection is presented. There were 7 (31.8%) children under the age of 1 year, 8 (36.4%) — 1—3 years old, 7 (31.8%) — 4—7 years old. Diagnosis of metapneumovirus infection was based on clinical data and on PCR analysis of nasopharyngeal mucus. Immunological studies in 10 patients included immunophenotype of patient's blood lymphocytes and analysis of the interferon system. Results. Among children under the age of 1 year 71.4 ± 17.1% were diagnosed with obstructive bronchitis and 28.6 ± 17.1% had pneumonia. In patients aged 1—3 years pneumonia was observed more often (55.6 ± 17.6%), obstructive bronchitis — less often (33.3 ± 16.7%), and in 11.1 ± 11.1% bronchitis occurred without symptoms of bronchial obstruction. In children aged 4—7 years only the upper respiratory tract was affected in 14.3 ± 13.2% of cases, 57.1 ± 18.7% developed bronchitis and 28.6 ± 17.1% — pneumonia. The immune system state was characterized by a low content of T-helpers (CD3 + CD4 + ) and NK-cells (CD3-CD16 + CD56 + ) detected in 7 (70%) and 5 (50%) patients respectively. IFNγ production was reduced in 70% of children and IFNα in 80%. Conclusion. Metapneumovirus infection in children in modern conditions is characterized by the frequent development of inflammatory changes in the bronchopulmonary system in the early stages of the disease. The disease severity was due to both manifestations of respiratory failure and severe symptoms of intoxication. Immunological studies revealed changes in the cellular link and the interferon system in all age groups.

Abstract 5953: DUSP6 is a novel target in neuroendocrine tumors

Abstract Background: Neuroendocrine tumors (NETs) are rare malignancies derived from enterochromaffin cells of the diffuse neuroendocrine system and most frequently observed in the gastrointestinal tract and bronchopulmonary system. Surgery is the major treatment for localized NETs. In high-grade NETs, treatment opportunities include chemotherapeutic drugs such as temozolomide (TEM), and capecitabine and small-molecule targeted therapies such as everolimus or sunitinib. Despite promising initial responses, most patients develop therapy resistance by unknown mechanisms. Therefore, there is a pressing need to apprehend the mechanisms of resistance to improve the therapeutic efficacy of the current treatments. Phosphatases are emerging and novel targets in human malignancies and their modulation yields significant anti-tumor activities. Dual specificity phosphatase 6 (DUSP6) is a MAPK phosphatase and mainly binds to and dephosphorylates extracellular signal-regulated kinase (ERK)1/2. DUSP6 expression is increased in several malignancies, correlating with distant metastases and a worse clinical outcome. Moreover, DUSP6 mediates resistance to certain chemotherapeutics and small molecular tyrosine kinase inhibitors and its blockade increases therapeutic sensitivity. The current study aimed to investigate the contribution of DUSP6 to therapy resistance in the NET models. Material and Methods: Using Western blot analysis, the expression of DUSP6 was measured in 8 clinical samples of small bowel neuroendocrine tumors, the NET cell lines BON-1, H69, IMR-32, QGP and H524 and two PDX models, 1452 (rectal neuroendocrine) and 913 (pancreatic neuroendocrine). The effects of DUSP6 depletion on cell viability were explored using a pharmacological inhibitor, BCI, and its siRNA-mediated knockdown. Moreover, BCI-mediated apoptotic cell death was measured by an annexin V/PI staining assay. Results: DUSP6 expression was positive in 5 out of 8 clinical samples, 4 NET cell lines and both the PDX models. BCI treatment induced an apoptotic response in the NET models and synergistically increased sensitivity to TMZ and cisplatin in 1452 cells., RNAi-mediated depletion of DUSP6 also increased sensitivity to sunitinib and triggered TMZ-induced apoptotic cell death in 1452 cells, which was associated with changes in (O6-Methylguanine-DNA-methyltransferase) MGMT expression. These findings suggest that DUSP6 is an important therapeutic target in neuroendocrine tumors and its blockade is a promising therapeutic approach to enhance the therapeutic index of current treatments. Citation Format: Majid Momeny, Vahid Khalaj, Solmaz AghaAmiri, Po Hien Ear, Servando Hernandez Vargas, Sukhen Ghosh, Ali Azhdarinia. DUSP6 is a novel target in neuroendocrine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5953.

The role of nanoparticles of industrial aerosols in the formation of occupational bronchopulmonary pathology

The significant prevalence of industrial aerosols with unintentional nanoparticles and the increasing use of engineering nanoparticles in modern production determine the relevance of research on the patterns of interaction with the human bronchopulmonary system. Unintentional nanoparticles are formed during various production processes: melting and welding of metals, combustion, crushing, grinding of minerals, plasma processing of materials. Engineering nanoparticles are released into the air of the work area during their production or use in any technological processes.
 The respiratory system, as a barrier organ, is most vulnerable to the effects of adverse environmental factors. At the same time, nanoparticles are the least studied component of industrial aerosols. In order to systematize data on the role of nanoparticles in the development of occupational bronchopulmonary pathology, the authors conducted a literature review.
 The size determines the features of the physical, chemical and biological properties of nanoparticles. They have high values of the ratio of surface area to volume, total surface area, which leads to an increase in reactogenicity and penetrating power. The pathogenic properties of nanoparticles depend on the chemical composition, shape, curvature of the surface, structure, charge, mass concentration, total surface area of the particles, and exposure time.
 The multidimensionality of hygienic characteristics determines the complexity of hygienic rationing and monitoring of nanoparticles. To date, safe exposure levels have not been established. When interacting with cells of the respiratory tract, nanoparticles induce the following cellular and molecular mechanisms: oxidative stress, inflammation, violation of the epithelial barrier, autophagy and dysfunction of lysosomes, stress of the endoplasmic reticulum, apoptosis, senescence, fibrosis, endothelial dysfunction, DNA damage. This leads to the development of interstitial pneumonitis, pulmonary fibrosis and obstructive disorders, and an increase in the activity of allergic inflammation. All these mechanisms are present in the pathogenesis of occupational lung diseases. Under the influence of nanoparticles of various chemical compositions, separate phenotypes of occupational chronic obstructive pulmonary disease are formed. There is a lack of epidemiological studies of the possible etiological role of nanoparticles. Nanoparticles of industrial aerosols are a significant factor in the development of occupational diseases of the bronchopulmonary system and have a significant impact on the formation 
 of phenotypes.

Broncho-obstructive syndrome in pediatrician’s practice (clinical cases)

Background. With the development of broncho-obstructive syndrome (BOS), spasm, edema, hypercrinia and bronchial dyscrinia occur. Increasing airflow resistance can complicate the course of diseases of the respiratory system. Broncho-obstructive syndrome coexists many pathologies, including cardiovascular diseases, gastrointestinal diseases and other abnormal developments of internal organs. The causes of this syndrome are diverse, including bronchial asthma, abnormal developments of the bronchopulmonary system, gastroesophageal reflux, cystic fibrosis and congenital heart diseases. The purpose of this study was to analyze and describe clinical cases of pediatric patients with BOS.Clinical cases description. The article presents clinical cases of patients who were treated at the State Budgetary Healthcare Institution of Republic of Crimea “Republic Children’s Clinical Hospital” at different times, who developed BOS against the background of Nijmegen Breakage Syndrome and aspiration of a foreign body (feather from a pillow) into the bronchi. Both clinical cases show the importance of comprehensive, and most importantly, timely diagnostic procedure. In clinical case No. 1, the medical history of patient N. with Nijmegen Breakage Syndrome is described. The pathology was revealed owing to a comprehensive diagnostic procedure. Representatives of patient N. appealed to the State Budgetary Healthcare Institution of Republic of Crimea “Republic Children’s Clinical Hospital” in connection with the development of symptoms of bronchial obstruction. Clinical case No. 2 describes the untimely diagnosis of a radiolucent bronchial foreign body. In this situation, the ambiguity of the clinical picture and, as a result, the search for other pathologies cost the child his life.Conclusion. Broncho-obstructive syndrome is associated with a variety of pathologies that are not limited to problems with the respiratory system. It is important to be able to identify symptoms in patients that will indicate the cause of the developed BOS.

Bronchopulmonary system within the confines of post-COVID-19 syndrome: literature review

The purpose of this review is to describe the available scientific data on the post-COVID-19 syndrome, formulate the main approaches to classification, determine the potential mechanisms of its pathogenesis, as well as determine the mechanisms of the occurrence of bronchopulmonary system pathology within the framework of the post-COVID-19 syndrome. It is known that long-term persistence of COVID-19 symptoms significantly reduces the quality of life of patients through the direct or indirect effect of the SARS-CoV-2 virus on a number of organs and systems. The review examines in detail the possible pathogenetic mechanisms of the post-COVID-19 syndrome, describes and studies the most common consequences of acute COVID-19, taking into account the severity of the disease, including diseases of the respiratory system, in particular interstitial and broncho-obstructive diseases. Particular attention is paid to the above problems in order to describe and structure the available scientific data on lung diseases within the framework of the post-COVID-19 syndrome. It should be noted, however, that there are very few studies on pathogenesis of changes in the bronchopulmonary system in the post-COVID-19 period. The bulk of them affect only individual manifestations of diseases of the respiratory system, in particular cough and shortness of breath, and are not aimed at determining causeand-effect relationships and the relationship of these symptoms to a specific nosology. Taking into consideration the continued high incidence of COVID-19, there is no doubt that additional studies of bronchopulmonary manifestations of post-COVID-19 syndrome should be conducted. Information from the databases PubMed, eLibrary, Scopus, Jstor was used as literary sources.

Клиническое значение интегральной регистрации маркеров эндотоксического иммунитета и колонизационной резистентности буккальных эпителиоцитов при рецидивирующем бронхите у подростков

Recurrent bronchitis (RB) occupies one of the key places in the structure of nonspecific diseases of the respiratory tract and remains a significant medical and social problem in healthcare. The purpose — to investigate and evaluate the clinical significance of integral registration of markers of endotoxic immunity and colonization resistance of buccal epithelial cells (BE) in RB in adolescents. Material and methods. The study included 117 children (12–17 years old), including 78 with RB — the main group, 29 with acute bronchitis (AB) — the comparison group and 23 conditionally healthy children — the control group. The analysis of anamnestic, clinical, paraclinical data, verification of etiologically significant viruses, registration of artificial colonization of buccal epithelial cells (BE), colonization index (CI), micro-LAL test were carried out. Statistical processing of the results was carried out using the SPSS program. Results. A significant difference in markers of colonization resistance and anti-endotoxin protection was revealed in recurrent inflammation in the respiratory tract in comparison with AB in peers. In RB, the initial degree of Candida albicans adhesion to BE was significantly higher in relation to AB (p = 0.0427) and upon discharge from the hospital did not reach normative values, being significantly different from patients with AB (p = 0.0391). The high index of artificial colonization indicates the activation of allochthonous flora and disruption of the microbiota in the oral cavity, which negatively affects the body reactivity. In patients with RB, the titer of antiglycolipid antibodies significantly decreased and in 75% the values did not return to normal, while in AB they did not differ from the control. High levels of endotoxin were noted in RB compared to AB (p = 0.0317). Such patients were diagnosed with a more severe course of the disease with symptoms of endogenous intoxication and a long hospitalization period. Using the method of correlation analysis, a high direct relationship was established between artificial colonization and endotoxin concentration (r = 0.71). The relationship between these parameters in AB was significantly less pronounced (r = 0.3). The results obtained indicate close integration and mutual modulation of the local oral immunity and antiendotoxin defense. Conclusion. Integral registration of the markers of reactivity of specific anti-endotoxin immunity and colonization resistance reflect the severe inflammatory process in the respiratory tract and predict the risk of a chronic pathological process in the bronchopulmonary system.

Деякі особливості ендокринного статусу у реконвалесцентів після COVID-19 та його зміни під впливом відновлювального лікування

Abstract. The aim — to study the thyroid hormones and cortisol levels in convalescents after COVID-19, including patients with chronic obstructive pulmonary disease (COPD) and their possible changes under the influence of recovery treatment. Materials and methods. 83 convalescents after COVID-19 (with manifestations of COVID pneumonia in the acute period) aged 32–67 years, who had no history of thyroid or adrenal glands lesions’ manifestations were examined. 29 of them had COPD (GOLD II-III). Patients began the course of rehabilitation within 1–3 weeks after inpatient treatment. Тhe levels of thyroid-stimulating hormone (TSH), total fractions of thyroid hormones (thyroxine — T4 , triiodothyronine — T3 ), cortisol as well as the level of interleukin-8 (IL-8) were determined in blood serum. Assessment was carried out by immunoenzymatic method at the beginning of recovery treatment and after it (within 21–22 days). Recovery treatment included the necessary basic anti-inflammatory and broncholytic therapy (for patients with COPD) and a physiotherapeutic complex, which included the use of haloaerosoltherapy (HAT) — dry aerosol media with certain concentration and dispersion (18-20 sessions per course) and singlet oxygen therapy (12 procedures per course). Results. Before treatment significantly higher levels of all studied indices compared to control were found in both groups of patients (without history of COPD and patients with COPD). Certain change of the inverse relationship between the values of TSH and T4 , T3 was noted, which probably indicates the presence of maladaptive thyroid syndrome. The obtained results can be interpreted as a consequence of systemic immune activation caused by SARS-CoV 2 infection and as a result of intensive treatment in the acute period. These changes took place on the background of a significant IL-8 level increase. A correlation between the levels of IL-8 and TSH (r=0.43) was revealed, which indicates a certain dependence between stimulation of thyroid gland function and the severity of the inflammatory process. Thyroid hormone levels in convalescents after COVID-19 without COPD (1st group) and convalescents after COVID-19 with COPD history (2nd group) were compared. Direction of changes in the thyroid hormones levels in both groups was similar, but the increase of TSH and T4 levels in the 2nd group was significantly higher and took place on the background of a higher IL-8 level. Studies of cortisol secretion in the examined groups showed a moderate, but reliable increase in its levels compared to the control by 1.2 and 1.4 times respectively. This may be related to both activation of the adrenal cortex during the convalescence and the consequences of therapy in the acute period of COVID-19. Taking into account received data, as well as the analysis of individual deviations of the studied indices, these changes should be considered as a non-thyroidal illness syndrome (NTIS) and dysfunctional adrenal disorders. The applied recovery treatment had a corrective effect on the thyroid and adrenal functions. Thus, by the end of treatment, the levels of cortisol and T3 reached the control level on the background of a significant decrease of IL-8 level in both groups of patients. Positive changes in thyroid function in convalescents after COVID-19 without COPD history were more pronounced. Conclusions. In convalescents after COVID-19 thyroid and adrenal dysfunctional disorders were observed, they were more pronounced in patients with COPD and directly correlated with an increase of pro-inflammatory IL-8 level. Rehabilitation treatment based on haloaerosoltherapy, which is aimed at bronchopulmonary system sanation and reduction of inflammatory process, contributes to the recovery of thyroid and adrenal function. Positive effect is more pronounced in patients without a history of chronic bronchopulmonary pathology.

Neuroendocrine tumors of the bronchopulmonary system and thymus

.

The predicting value of circular DNA particles of T- and B-cell receptors for the dismal acute period outcomes and the disease severity of COVID-19 infection

The pandemic of the new coronavirus infection COVID-19, caused by the SARS-CoV-2 virus, continues to be a serious problem for the entire global community. Currently, most patients experience mild COVID-19, with only about 20% of those infected requiring hospitalization. The severe course of COVID-19 is most often associated with damage to the patient’s bronchopulmonary system by the virus and serious abnormalities, including damage to the air-hematological barrier, systemic inflammation, dysfunction of the immune system and the addition of secondary infections. Severe disease and poor outcome in hospitalized patients with COVID-19 may be associated with lymphopenia in combination with neutrophilia. Restoring the number of lymphocytes is important to improve the prognosis of the patient’s outcome. Patients with COVID-19 experience an immune imbalance where systemic inflammation and dysfunction of circulating T and B cells lead to more severe disease. TREC/KREC analysis can characterize the function of the central organs of the immune system and its relationship with clinical and laboratory data. Decreased TREC/KREC levels were observed in patients with unfavorable disease outcomes compared to patients with favorable disease outcomes. Additionally, a higher neutrophil to lymphocyte ratio was found. Levels of TREC and KREC in the blood negatively correlate with the neutrophil-lymphocyte ratio. Thus, the TREC/KREC assay is a potential prognostic marker for assessing the severity and outcome of COVID-19.

Microflora of the lungs in health and disease, the impact of vaccination

The development of new methods for diagnosing infectious diseases, such as polymerase chain reaction, sequencing, and mass spectrometry, has made it possible to expand our understanding of the microflora of the human body in general and of the respiratory tract in particular. The most common microorganisms in lungs include Proteobacteria (Pseudomonas spp., Haemophilus spp.), Bacteriodetes (Prevotella spp., Porphyromonas spp.) and Firmicutes (Veillonella spp., Streptococcus spp.). Pathological processes in the lower respiratory tract change the microbiome. Consequently, Moraxella, Haemophilus, and Acinetobacter microorganisms are found in patients with chronic obstructive pulmonary disease. The main causative agents of community-acquired pneumonia include Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae and other enterobacteria. Atypical causative agents of pneumonia include Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. The wide prevalence of S. pneumoniae in the population confirms the need for vaccines to prevent the development of invasive and noninvasive forms of infection.The aim of the study was to analyze literature data on the structure of the normal microflora of the lung and to investigate its role in the development of pathological conditions.Conclusion. A growing body of research confirms the important role of the normal microflora of the respiratory tract. Vaccination against diseases of the bronchopulmonary system may reduce the incidence and mortality of pneumonia. However, the problem of community-acquired pneumonia is still relevant. In particular, the changes in the structure of the pathogens of this disease is of great interest. Vaccination against respiratory pathogens in combination with uncontrolled use of antibiotics during the pandemic of the new coronavirus infection could contribute to a change in the structure of both the lower respiratory microflora in general and the pathogens of bacterial community-acquired pneumonia in particular. The detection of a change in the predominant pathogen calls for revising etiotropic treatment and organizing planned prophylaxis if the appropriate vaccines are available.